Quality Control Procedures for High-Throughput Genetic Association Studies

Genome-wide association (GWA) studies provide an unbiased approach to discovering the role of genetic determinants of disease across the human genome. The case-control design, the most frequently used GWA study design employed to date, compares allele frequencies in affected patients to those of unaffected controls. Several large-scale GWA studies have identified numerous risk variants for celiac disease (CD). However, due to their low marker density, the early GWA arrays failed to adequately capture much of the genetic variance associated with CD. The Immunochip, a custom Illumina Infinium high-density array containing 196,524 common and rare polymorphisms, was developed to allow deep replication and fine mapping of the previously established GWA significant loci identified in 12 major autoimmune and inflammatory diseases, including CD. It has the advantage of allowing uniform sets of genetic markers to be compared across all diseases. This chapter describes the methods used to perform Immunochip genotyping and the bioinformatics steps necessary for quality control and analysis of the resulting data.